Abstract
Neurodegenerative diseases called tauopathies, such as Alzheimer’s disease (AD), frontotemporal dementia, progressive supranuclear palsy, and Parkinson’s disease, among others, are characterized by the pathological processing and accumulation of tau protein. AD is the most prevalent neurodegenerative disease and is characterized by two lesions: neurofibrillary tangles (NFTs) and neuritic plaques. The presence of NFTs in the hippocampus and neocortex in early and advanced stages, respectively, correlates with the patient’s cognitive deterioration. So far, no drugs can prevent, decrease, or limit neuronal death due to abnormal pathological tau accumulation. Among potential non-pharmacological treatments, physical exercise has been shown to stimulate the development of stem cells (SCs) and may be useful in early stages. However, this does not prevent neuronal death from the massive accumulation of NFTs. In recent years, SCs therapies have emerged as a promising tool to repopulate areas involved in cognition in neurodegenerative diseases. Unfortunately, protocols for SCs therapy are still being developed and the mechanism of action of such therapy remains unclear. In this review, we show the advances and limitations of SCs therapy. Finally, we provide a critical analysis of its clinical use for AD.
Highlights
INTRODUCTIONIn NCT01297218, the safety and effectiveness of stereotactic brain injection of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) were tested in mild to moderate Alzheimer’s disease (AD)
It has been estimated that over 50 million people live with dementia globally, a number set to increase to 152 million by 2050
Alzheimer’s disease (AD) is a neurodegenerative disease marked by irreversible neuronal death resulting in progressive and disabling impairment of cognitive functions, such as memory, language, reasoning, behavior, and executive function, which interfere with the essential daily activity of the person
Summary
In NCT01297218, the safety and effectiveness of stereotactic brain injection of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) were tested in mild to moderate AD. All these trials are using MSCs, either isolated from adipose tissue (NCT0 4388982 and NCT04228666), placenta (NCT02 899091), umbilical cord blood (NCT02054208), bone marrow (NCT03724136 and NCT02600130), or are from an unspecified source (NCT02833792) Due to their unique properties, such as rapid proliferation, high differentiation capacity, and ability to migrate into the site of damage, MSCs are increasingly being used for cell therapy and tissue regeneration [107]. More research and preclinical trials are still required to elucidate the mechanisms of action of SCs. Title Follow-up study of safety and efficacy NEUROSTEM clinical trial (NCT02054208) Alzheimer’s Autism and Cognitive Impairment Stem Cell Treatment Study (ACIST). A long-term follow-up study to obtain safety and efficacy data in subjects who completed phase 1/2a clinical trial of NEUROSTEM (human umbilical cord blood-derived mesenchymal stem cells).
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